Dose control system for injectable-drug delivery devices and associated methods of use

ABSTRACT

A dose monitoring system for mounting on an injection pen having a body and a dose setting wheel defined at the end of the body. The dose monitoring system includes a magnet configured to be attached to an outer surface of the dose setting wheel, a housing configured to be attached to an outer surface of the body of the injection pen, the housing includes an integrated control unit and at least one magnetometer in electrical connection with the integrated control unit, the integrated control unit, when the housing is mounted on the injection pen, being configured to register at least one magnetic field sensed by the at least one magnetometer when the magnet co-rotates with the dose setting wheel during setting of a dose by a user on the injection pen, the integrated control unit being further configured, when the housing is mounted on the injection pen, to calculate a dose set by the user of the injection pen from the at least one magnetic field registered with the integrated control unit.

CROSS-REFERENCE TO RELATED APPLICATION(S

This application is a Continuation of commonly owned US Pat. ApplicationSerial No. 15/746,422, entitled: DOSE CONTROL SYSTEM FOR INJECTABLE-DRUGDELIVERY DEVICES AND ASSOCIATED METHODS OF USE, filed on Jan. 21, 2018,the disclosure of which is incorporated by reference herein.

BACKGROUND

The present invention relates to the field of injectable-drug deliverydevices, and in particular, to dose control systems provided for suchinjectable-drug delivery devices.

Delivery devices for injectable drugs have been known for many years. Asdemands have progressed and evolved for more patient responsibility inthe management of their own individual treatments and medication plans,various drug delivery devices have been developed that allowed a user toself-inject their drug. This is particularly the case, for example, withinsulin, intended to treat the consequences of diabetes. However, otherdrugs also fall into this category, required for example, to addresspotentially life-threatening situations, and enabling immediateemergency injection of a required drug, such as anaphylactic shocktreatments, anti-coagulants, opioid receptor agonists and antagonists,and the like, to the extent that it has become a common occurrence forpatients suffering from, or susceptible to, such ailments to carry thesedevices around with them.

One of the known problems with the existing self-injector systems wasthat of dosage control. In previous generations of injectable-drugdelivery devices, such devices were equipped with mechanical means inorder to attempt to prevent or limit excessive dose injections, or overuse of the device, and the potentially serious consequences of suchabuse, misuse, or simply user error. Additionally, it was felt desirableto be able to inform the user how much of the drug they hadself-injected, so that there might be at least some visible cue as theinjected amounts, thereby facilitating management of the treatmentregime.

The main problems associated with the mechanical solutions proposed wasthat the necessarily over-complexified the structure of the drug deliverdevices, and quite often imposed a very strict or complicated modusoperandi on the user, which often could be different to that to whichthe user was accustomed, thereby leading to yet further manipulationerrors, lost drug doses, patient non-compliance, and numerous otherdifficulties.

To counter these difficulties, attempts were made to address the complexnature of purely mechanical solutions involving moving mechanical partsand mechanical interactions of small and fragile components, through theuse of contactless sensors and an information processing system builtinto the device to indicate the frequency and dose amounts of injectabledrug administered, wasted, purged or otherwise expelled from the drugdelivery device. This led to multiple different technical solutions,however, each one was geared to the specifics of the particularmanufacturer’s corresponding range of injectable-drug delivery devices.

For example, in US8708957B2, a drug delivery device for self-injectionof an injectable drug is disclosed comprising a sensor which is adaptedto generate pulses during injection as the delivery movements progress.The number of pulses accumulated during dose delivery correspond to thesize of the dose being delivered, whereas the frequency of the detectedpulses is proportional to the dose speed during injection.

In other embodiments, the sensor circuitry can include position sensorsadapted to monitor specific components of the drive mechanism which moveduring injection. The position sensors can be either linear sensors orrotary sensors, the particular choice of sensors being selected inaccordance with the specific design of the dose setting and injectionmechanism. For example, a linear position sensor can be provided thatmonitors the movements of the piston rod during injection.Alternatively, position sensors are provided which record the movementsof a component which moves in synchronism with the piston rod duringinjection. For example, a component being rotatably mounted in thedevice and which rotates during injection may be monitored by a rotaryposition sensor whereby the dosing speed may be calculated from therotary movement of the rotatably mounted component during injection.

EP1646844B2 discloses an injection device for administering andinjectable drug, the device comprising a non-contact measuring unit formeasuring a position between elements of a dosing device, and which canbe moved relative to one another, the measuring unti comprising amagneto-resistive sensor, fixed to a first element, opposite a secondmagnetizable element, movable relative to the first element, andembodied as a rotational element for measuring rotational position; anda magnetic device formed from a permanent magnet on the first element,and a second magnetizable element with a predetermined surface profilesuch that when the first and second elements are moved relative to eachother, a surface of the second element changes its distance from thepermanent magnet of the first element, whereby a measurable change inresistance is generated in the magneto-resistive sensor due to thechange in magnetic field. This is a fairly complex system with manyadditional moving parts built into the barrel, or body, of theinjectable-drug delivery device, leading to a greater risk of potentialfailure of the various components, or potentially interferinginteraction between the movements of the magnet and magnetizableelements, and the respective signals generated.

EP2428238A1 discloses an apparatus apparatus for measuring a dose in aninjector, comprising a number sleeve that passes through an injectorbody and is connected to the injector body to be spirally movable, apattern for dose measurement being formed on an outer periphery of thenumber sleeve; and the injector body comprising a sensor for sensing thepattern formed on the number sleeve when the number sleeve performs aspiral movement; and a controller for measuring a dose according to aspiral movement distance of the number sleeve through the sensor. Inthis device, a magnet is displaced spirally along the body of the drugdelivery device, which is provided with corresponding sensors located atvarious points along and around the longitudinal axis of the body of thedrug delivery device. Once again, this solution is extremely complex,and adds further complexity to an already complex drug delivery device.

WO 02/064196 A1 discloses an injection apparatus controlled by a closedswitch unit comprising integrated sensors which monitor selectedparameters of the apparatus. The closed switch unit is fixed within theinjection apparatus. At least two pairs of integrated Hall elements areused as the sensors. The Hall elements co-operate with a magnetized ringwhich alternately exhibits north and south poles. The ring is arrangedwithin a dosing means and is moved around the longitudinal axis of theinjection apparatus in accordance with a rotational movement for settinga product dosage. In order to measure the volume of a dosage setting, itis necessary to determine the rotational movement of the magnetic ringrelative to the closed switch unit.

US20060175427A1 discloses an injection apparatus comprising at least onepassive, non-contact sensor which can generate signals for detecting theposition of a setting element, the at least one passive, non-contactsensor comprising a magnetic switch or Reed contact. According to someembodiments of the present invention, a passive component such as amagnetic switch or Reed contact may be used as the sensor, as opposed tousing active components, such as optical recorders or Hall sensors. Nopower flows when the passive sensor is in its resting state due to thecircuit being interrupted by the magnetic switch or Reed contact. Thepassive, non-contact sensor generates digital signals, i.e. ON and OFF,which switch on or activate a measuring circuit and switch it off again,in order to detect the position of a setting element by counting theswitching-on and switching-off processes. The position of a settingelement such as a rotational position of a dosing unit can be detectedwithout energy, such as power, in order to ascertain whether a settingelement has been altered or not.

WO2013050535A3 discloses a system comprising a sensor assembly adaptedto measure a magnetic field, and a moveable element adapted to be movedrelative to the sensor assembly between two positions by a combinedaxial and rotational movement, the rotational movement having apre-determined relationship to the axial movement. A magnet is mountedto the moveable element and configured to generate a spatial magneticfield which relative to the sensor assembly varies corresponding to boththe axial and rotational movement of the magnet and thus the moveableelement. A processor is configured to determine on the basis of measuredvalues for the magnetic field an axial position of the moveable element.In this system, a magnetic field producing means is located on alongitudinal drive screw that is located within the body of theinjectable-drug delivery device, and the sensors are located along alongitudinal axis of said drug delivery device. It is noted that thewhole of this system is located once again within the main body of thedrug delivery device, in order for the magnetic field to be generated asclose as possible to the longitudinal axis along which the magnet moves,and the sensors.

WO2014161954A1 discloses a drug delivery system, wherein the housing ofthe drug delivery device further comprises, integrated inside saidhousing, a first rotational member adapted to rotate relative to thehousing corresponding to a set and/or expelled dose and comprising afirst force transmitting surface, a second rotational member adapted torotate relative to the housing corresponding to a set and/or expelleddose and comprising a second force transmitting surface, wherein atleast portions of the first and second force transmitting surfaces areadapted to engage each other during setting and/or expelling of a dose,wherein the first rotational member comprises a magnet producing amagnetic spatial field which varies corresponding to the rotationalmovement of the first rotational member, and wherein the firstrotational member is fully formed from a polymeric material containingmagnetic particles, the polymeric material having been magnetized toprovide a magnet producing the magnetic spatial field.

All of the above solutions involve a fairly complex arrangement ofvarious sensors and/or organisation of elements within the body of thedrug delivery device, which moreover generally imply having to modifysaid drug delivery device fairly substantially.

SUMMARY

Accordingly, it is an object of the invention to provide a dose controlsystem that can function with any of the currently availableinjectable-drug delivery devices, but which will also function withfuture designs of such injectable-drug delivery devices, where they relyon the general pen-shape auto-injector design, in which the drugdelivery device comprises a substantially elongate drug delivery body,at least one injectable drug held by the body, the body having a distaland proximal extremity. Additionally, it is another object of thepresent invention to provide such a dose control system which does notrequire substantial modification of the injectable-drug delivery deviceor the way in which it functions for the user, i.e. its modus operandi,when compared to a like, off-the-shelf drug delivery device. It is yetanother object of the present invention to provide a dose control systemthat is removably mounted on said injectable-drug delivery devices, suchthat the drug delivery devices can be exchanged, for example, in case ofdamage to the drug delivery device or malfunction in the drug deliverydevice, or simply because some drug delivery devices are configured toonly deliver a small range of available doses of drug, and it isdesirable to be able to switch to another drug delivery device that hasa different range of available doses of drug. These and other objectswill become apparent from the various embodiments as indicated anddetailed hereinafter.

Accordingly, one embodiment of the present invention is a dose controlsystem adapted for an injectable drug delivery device, the drug deliverydevice comprising a substantially elongate drug delivery body, at leastone injectable drug held by the body, the body having a distal andproximal extremity, wherein the dose control system comprises:

-   three-dimensional magnetic field producing means for producing a    magnetic field along three axes (x,y,z);-   magnetic field detection means configured to detect changes in at    least the magnetic field produced by the three-dimensional magnetic    field producing means;-   displacement detection means configured to measure a relative    displacement or relative movement of the drug delivery device, and-   an integrated control unit, wherein the integrated control unit is    connected to the magnetic field detection means, and to the    displacement detection means, for processing information received    from both the magnetic field detection means and the displacement    detection means;

wherein:

-   the three-dimensional magnetic field producing means is configured    to effect a rotating coaxial displacement around, and optionally    along, a longitudinal axis of the drug delivery system;-   the magnetic field detection means are located along said    longitudinal axis; and-   the three-dimensional magnetic field producing means is removably    located at, or near, a proximal extremity of the body of the drug    delivery device.

According to another embodiment of the dose control system of theinvention, said dose control system is removably mounted to an exteriorperipheral surface of said injectable drug delivery device.

According to yet another embodiment of the dose control system of theinvention, the drug delivery device comprises a dose selector shaft, andthe three-dimensional magnetic field producing means is mounted aroundsaid dose selector shaft at a proximal extremity thereof.

In yet another embodiment of the present invention, the dose selectorshaft is configured to operate a displacement of the three-dimensionalmagnetic field producing means relative to the drug delivery device,whereby said three-dimensional magnetic field producing means isconfigured to move both in a proximal direction away from, and in adistal direction towards, the body of the drug delivery device.

In another embodiment according to the invention, the magnetic fielddetection means and the displacement detection means are removablymounted on the body of the drug delivery device.

In still yet another embodiment of the dose control system according tothe invention, the magnetic field detection means and the displacementdetection means are removably mounted on the body of the drug deliverydevice, substantially at a distal extremity thereof.

In yet another embodiment according to the invention, the magnetic fielddetection means is further configured to detect the earth’s magneticfield (EMF).

In another embodiment of the present invention, the magnetic fielddetection means comprises at least one magnetometer.

According to another embodiment of the present invention, the magneticfield detection means comprises at least two magnetometers.

In yet another embodiment of the present invention, the magnetic fielddetection means comprises at least a first and second magnetometers,wherein the first magnetometer and the second magnetometer areconfigured to operate in parallel, both magnetometers simultaneouslydetecting any changes in magnetic field, as the three-dimensionalmagnetic field producing means is displaced proximally away from ordistally towards them.

According to yet another embodiment, the magnetic field detection meanscomprises at least a first and second magnetometers, wherein the firstmagnetometer and the second magnetometer are configured to operate inseries, whereby the first magnetometer detects changes in magnetic fielduntil a predetermined value of magnetic field is detected, and then thesecond magnetometer is activated to detect changes in magnetic fieldbeyond said predetermined value, as the three-dimensional magnetic fieldproducing means is displaced proximally away from or distally towardsthem.

In still yet another embodiment of the invention, the displacementdetection means comprise at least one accelerometer configured todetect:

-   the relative movement of acceleration caused by a vibration of the    dose selector shaft; and/or-   a positional movement of the drug delivery device between an    injection position and a purge position.

In a further embodiment of the invention, the dose control systemfurther comprises communication means configured to enable communicationof information from the integrated control unit with a remote and/orlocal data processing system.

In yet another embodiment of the invention, the remote and/or local dataprocessing system comprises a smartphone application.

In still another embodiment of the invention, the dose control systemfurther comprises a unique identifier that is communicated to the remoteand/or local data processing system.

In another embodiment of the invention, the dose control system furthercomprises temperature detection means.

In another embodiment of the invention, the dose control system furthercomprises time determination means.

In a further embodiment of the invention, the dose control systemfurther comprises autonomous power supply means.

In still yet another embodiment of the present invention, said dosecontrol system is configured to permit an unhindered or unchanged modusoperandi of said drug delivery system when compared to an off the shelfinj ectable-drug delivery device.

In yet another embodiment of the present invention, said magnetic fielddetection means, said displacement detection means, said integratedcontrol unit, said autonomous power supply means, and said communicationmeans are all located within a first removably mountable housingconfigured to removably be mounted on, and encase the body of saidinjectable-drug delivery device, and said three-dimensional magneticfield producing means is located within a second housing configured toremovably be mounted on, and surround the dose selector shaft of saidbody of said injectable-drug delivery device.

In yet another embodiment according to the present invention, there isprovided a method for improving observance of treatment in an injectabledrug administration regime, said method comprising:

-   providing a dose control system removably mounted to an exterior    peripheral surface of an injectable drug delivery device comprising    a substantially elongate drug delivery body, at least one injectable    drug held by the body, the body having a distal and proximal    extremity;-   determining a dose set by the user via manipulation of the dose    control system; and-   determining an operational status of the drug delivery device;-   relaying information obtained from said dose determination or said    operational status determination to a remote and/or local data    processing system.

In yet another embodiment, the method for improving observance oftreatment in an injectable drug administration regime, said methodfurther comprises:

-   validating an actual injected dose of injectable drug.

In still yet another embodiment, the method for improving observance oftreatment in an injectable drug administration regime, comprises adetermination of a user-set dose, wherein said determination is effectedby:

-   rotating a three-dimensional magnetic field producing means,    removably mounted on a dose selector shaft, around a longitudinal    axis of said body of the drug delivery device;-   detecting changes in magnetic field produced in at least two    orthogonal dimensions, and preferably in three orthogonal dimensions    (x,y,z) via magnetic field detection means removably mounted on the    body of the drug delivery device;-   correlating, via an integrated control unit, the changes in magnetic    field detected by the magnetic field detection means, with an    angular position of the rotated three-dimensional magnetic field    producing means;-   correlating said angular position to a corresponding dose.

In another embodiment of the method for improving observance oftreatment in an injectable drug administration regime, a determinationof an operational status of the drug delivery device comprises one ormore of the following:

-   detecting a positional movement of the drug delivery device via    displacement detection means removably mounted on the body of the    drug delivery device to determine whether the device is in a purge    position, or an injection position;-   detecting a temperature of the drug held by the body of the drug    delivery device via temperature detection means and determining    whether said temperature is within acceptable operating limits for    an administration of the drug;-   detecting a level of autonomous power supply; and-   detecting whether the dose control system is in a hibernated or    awake state.

In yet another embodiment of the method for improving observance oftreatment in an injectable drug administration regime, wherein avalidation of an actual injected dose of injectable drug is effected by:

-   detecting a validation of a dose setting via displacement detection    means removably mounted on the body of the drug delivery device,    said validation being created by a clicking action of the user on a    distal extremity of the dose selector shaft;-   measuring elapsed time between said clicking action of the user and    actual injection of the drug;-   correlating the elapsed time between said clicking action of the    user and the time at which actual injection occurs with an    acceptable set of stored values to validate the selected dosage as    the actual injected dosage of injectable drug.

In still yet another embodiment, the method for improving observance oftreatment in an injectable drug administration regime is further definedwherein a determination of a user-set dose is effected by:

-   rotating the three-dimensional magnetic field producing means,    removably mounted on a dose selector shaft, around a longitudinal    axis of said body of the drug delivery device, wherein each rotatory    movement generates a series of one or more audible clicks, each    rotational click also producing a vibration and corresponding    relative displacement movement in the device;-   the relative displacement movements in the device produced by each    rotational click being detected by the displacement detection means.

In another embodiment of the method for improving observance oftreatment in an injectable drug administration regime, each rotationalclick of the dose selector shaft corresponds to a rotationaldisplacement of the magnetic field producing means around thelongitudinal axis of the device.

In still yet another embodiment of the method for improving observanceof treatment in an injectable drug administration regime, thedisplacement detection means have a maximum resolution comprised between1 Hz and 2 KHz.

In yet a further embodiment of the method for improving observance oftreatment in an injectable drug administration regime, the displacementdetection means are configured to detect accelerational displacements offrom about 0.5 G to about 16 G.

In another embodiment of the method for improving observance oftreatment in an injectable drug administration regime, the magneticfield detection means are configured to detect changes in magnetic fieldof from about 0.5 gauss to about 32 gauss.

As mentioned in the various embodiments of the invention, the dosecontrol system comprises means for producing a three-dimensionalmagnetic field. The magnetic field producing means produces a magneticfield that extends over three mutually perpendicular axes, x, y and z.As will be seen with regard to the detailed description of theinvention, this three-dimensional magnetic field is used to calculate anangular rotational position in the dose control system of the magneticfield producing means in relation to the longitudinal axis of the bodyof the injectable-drug delivery device, and when that angular rotationalposition is known, calculate the corresponding dose.

Various means for producing a magnetic field can be used in the presentinvention, for example, classical magnets, electromagnets, mixedmaterial material magnets, and the like all of which are generally knownin the art. Such magnets are typically made from magnetizable materials,having magnetic or paramagnetic properties, whether naturally or when anelectric or other energizing flow traverses or affects said material toproduce or induce a magnetic field in said material. Suitable materialscan be appropriately selected from :

-   ferrite magnets, especially sintered ferrite magnets, for example,    comprising a crystalline compound of iron, oxygen and strontium ;-   composite materials consisting of a thermoplastic matrix and    isotropic neodymium-iron-boron powder;-   composite materials made up of a thermoplastic matrix and    strontium-based hard ferrite powder, whereby the resulting magnets    can contain isotropic, i.e. non-oriented, or anisotropic, i.e.    oriented ferrite particles ;-   composite materials made of a thermo-hardening matrix and isotropic    neodymium-iron-boron powder;-   magnetic elastomers produced with, for example, heavily charged    strontium ferrite powders mixed with synthetic rubber or PVC, and    subsequently either extrused into the desired shape or calendering    into fine sheets ;-   flexible calendered composites, generally having the appearance of a    brown sheet, and more or less flexible depending on its thickness    and its composition. These composites are never elastic like rubber,    and tend to have a Shore Hardness in the range of 60 to 65 Shore D    ANSI. Such composites are generally formed from a synthetic    elastomer charged with strontium ferrite grains. The resulting    magnets can be anisotropic or isotropic, the sheet varieties    generally having a magnetic particle alignment due to calendaring ;-   laminated composites, generally comprising a flexible composite as    above, colaminated with a soft iron-pole plate ;-   neodymium-iron-boron magnets;-   steels made of aluminium-nickel-cobalt alloy and magnetized ;-   alloys of samarium and cobalt.

Of the above list of magnetic field producing means, those comprising apolymer matrix, e.g. a thermopolymer matrix, and magnetic ormagnetizable particles embedded therein, have been found to giveparticularly good results, as they can be injection moulded into variousdesired configurations, and provide a magnetic field of suitablestrength, which for the present invention is a magnet producing amagnetic field of between approximately 0.5 gauss and about 32 gauss.These products are generally also known as plastomagnets, a range ofwhich are available from Arelec (France).

As will be seen in the detailed description given hereafter, the threedimensional magnetic field producing means are substantially annularshaped. By “substantially annular shaped”, it is to be understood thatthe magnetic field producing means defines a general ring shape, whichcould be circular, elliptoid, or even any suitable polygonal shape. Insome instances, the magnetic field producing means could be made up ofone or more separate or discontinuous segments of magnetic fieldproducing material, for example, arcuate, quarter-spherical, orhemi-speherical, each with at least one pair of opposing magnetic poles.It is however preferred that the substantially annular ring shapedthree-dimensional magnetic field producing means be made of a singleblock of magnetic or magnetizable material, and whilst it is possible toprovide a multipolar block of magnetic field producing means, it ispreferred to have only two magnetic poles, one being the opposite inpolarity of the other, in the three-dimensional magnetic field producingmeans.

The three-dimensional magnetic field producing means of the presentinvention is configured to effect a rotating coaxial displacementaround, and optionally along, a longitudinal axis of the drug deliverysystem. The rotating displacement coincides with that of a dose selectorshaft, meaning that turning the magnetic field producing means aroundthe longitudinal axis causes said shaft to rotate in the same direction,and to generate a clicking sound. Additionally, as is generallyapplicable to drug delivery devices equipped with such dose selectorshafts, the magnetic field producing means can translate longitudinallywith the dose selector shaft away, i.e. proximally, from the proximalextremity of the body of the drug delivery device, when increasing thedose to be injected. Conversely, the magnetic field producing means willrotate in the opposite direction and can translate longitudinally alongthe longitudinal axis of the device distally, back towards the proximalextremity of the device as the dose is reduced. In another embodimentaccording to the invention, the dose selector shaft is not configured toenable longitudinal translation, meaning that the dose selector shaft issimply configured to rotate about the longitudinal axis, and that thisrotational movement defines the doses selected, whether clockwise orcounter-clockwise. The dose control system can accordingly be adapted tosuch a drug delivery device also.

In addition, the magnetic field producing means is dimensioned toprovide sufficient magnetic field to be detected by the magnetic fielddetection means, but also so as to not add extra volume to the dosecontrol system, and thereby hinder the user or usage of the drugdelivery device in normal operation when compared to a drug deliverydevice that has no such dose control system according to the invention.

In the dose control system according to the present invention, magneticfield detection means are present and configured to detect changes in atleast the magnetic field produced by the three-dimensional magneticfield producing means. Additionally, said magnetic field detection meanscan also be configured to detect the earth’s magnetic field (EMF), whichis always present on earth, and which varies slightly from place toplace. One of the reasons to include detection of the earth’s magneticfield is to be able to exclude any interference caused by said field andthe changes detected in the magnetic field produced by the magneticfield production means. The magnetic field detection means are usedmainly to measure changes in magnetic field produced by movement of themagnetic field producing means, and as will be seen from the detaileddescription, to calculate an angular rotational position of the magneticfield producing means in order to determine a selected dose foradministration via the injectable-drug delivery device. There arenaturally other means suitable for detecting angular positionsassociated with rotational movements, for example, potentiometers, codedwheels and the like, however both of the latter are generally toovoluminous for dose control systems such as the one according to theinvention, particularly in regard to the fact that the system accordingto the invention is intended to be removably mounted to theinjectable-drug delivery device, e.g. an autoinjector pen, and thuscumbersome and voluminous additional components are generally notpreferred.

Other means of detecting magnetic fields to determine a rotationalangular position are also known in the art. For example,magneto-resistors are a well known means, some of which are used in theprior art systems. Such magneto-resistors are often designated by theirabbreviations, e.g. AMR, GMR, TMR sensors which designate the physicalmechanisms by which these sensor components function. Giantmagnetoresistance (GMR) is a quantum mechanical magnetoresistance effectobserved in thin-film structures composed of alternating ferromagneticand non-magnetic conductive layers. Anisotropic magnetoresistance, orAMR, is said to exist in materials in which a dependence of electricalresistance on the angle between the direction of electric current anddirection of magnetization is observed. Tunnel magnetoresistance (TMR)is a magnetoresistive effect that occurs in a magnetic tunnel junction(MTJ), which is a component consisting of two ferromagnets separated bya thin insulator. Resistors that use these various properties are knownper se. Whilst their use is possible in the present dose control systemas the means for detecting the magnetic field and changes therein asproduced by displacement of the magnetic field producing means and/orthe earth’s magnetic field, they are limited to dose control systems inwhich the magnetic field producing means, of corresponding equivalentdimensions and magnetic field strength, is moved away from said GMR,AMR, or TMR sensors by no more than about 25 mm. This would explain whymost of the known prior art solutions have always integrated theirsensors and magnetic field producing means within the body of the drugdelivery device, in a grouped fashion, over a short distance, or elsehad to provide four or more aligned magneto-resistive sensors in orderto cover the whole available distance of the piston length to cover allpossible detectable and usable doses of the drug delivery device, whichin many cases can have a maximum path length of up to 40 mm.

In light of the above, the dose control system of the present inventionpreferably uses magnetometers, for example, at least one magnetometer,and more preferably at least two magnetometers. These magnetometersdiffer from the GMR, AMR or TMR sensors in that they directly measuremagnetic field strength, and changes therein. Magnetometers measuremagnetic fields in two main ways: vector magnetometers measure thevector components of a magnetic field and total field magnetometers orscalar magnetometers measure the magnitude of the vector magnetic field.Another type of magnetometer is the absolute magnetometer, whichmeasures the absolute magnitude or vector magnetic field, using aninternal calibration or known physical constants of the magnetic sensor.Relative magnetometers measure magnitude or vector magnetic fieldrelative to a fixed but uncalibrated baseline, and are also calledvariometers, used to measure variations in magnetic field. A suitableand preferred magnetometer for use in the dose control system accordingto the present invention is an ultra low-power high performance threeaxis magnetic sensor, available from ST Microelectronics, for examplethe LIS3MDL. Whilst it is preferred that the magnetometer be able todetect changes in magnetic field over three perpendicular axes, it isalso envisaged to be able to measure changes in magnetic field over justtwo of the three axes of magnetic field produced by thethree-dimensional magnetic field production means. A device such as theLIS3MDL can be configured to detect magnetic fields across a full scaleup to ±4 / ±8 / ±12 / ±16 gauss, however, it could also be useful andadvantageous to use magnetometers that are capable of detecting evenhigher magnetic fields, e.g. 32 gauss. In the present invention, it thusis preferred that the magnetometer be configured to detect magneticfields of from about 0.5 gauss to about 32 gauss.

As mentioned above, the dose control system of the present inventionalso comprises displacement detection means configured to measure arelative displacement or relative movement of the drug delivery device.Such displacement detection means could typically use sound, forexample, as a way of registering movements in a dose selector shaft, assuch dose selector shafts are often constructed so as to make a clickingnoise via a toothed cylinder ratcheting against, for example, the innerwall or a corresponding depression or cavity of said inner wall matchingthe tooth, which when rotated about the longitudinal axis of the drugdelivery device, drives the tooth in and out of said depression orcavity and causes an audible click. The clicking sound therebyfacilitates any other visual cues that might be given to the user. Eachclick generally represents an angle of rotation of the shaft about thelongitudinal axis, irrespective of direction of rotation, andcorresponds to a selected dose. However, if the dose selector shaft isturned very quickly, or clockwise and counterwise in quick succession,or vice-versa, it becomes almost impossible to know which dose has beenselected just by the audible cue of the clicks alone. Thus, theapplicants have chosen to measure the movements induced by thevibrations of the dose selector shaft when it is turned and generatesone or more clicks, as the vibration provides a relative movement thatcan be detected. These movements correspond to tiny accelerations, andcan be detected and measured appropriately through the use ofcorresponding accelerometers, which are the preferred means for thedisplacement detection means of the present invention, as they can beconfigured to detect accelerational movements along three perpendicularaxes, and the time between movements can be measured so as to compareagainst a predetermined standard set of accelerational movements forsaid drug delivery devices and which correspond to normal usage of thedevice at the various stages of its use for administering an injectableproduct. For example, when the drug delivery device is in asubstantially horizontal position, or in either of the substantiallyvertical positions, i.e. purge or injection, the accelerometer detects asubstantially constant signal of low frequency vibrations, which can beused as a base line for the device. Whenever the dose selector shaft, oran end button to prime the injector, or effect injection, is activated,or rotated, the vibrations generated thereby are captured as highfrequency spikes compared to the low frequency baseline. These highfrequency vibrations can be sampled and analyzed the results of whichare then used to determine which operations have been undertaken by auser. Whilst there exist many different types of accelerometer on themarket, the applicants have a preference for a low-g three-axisaccelerometer, such as those available from ST Microelectronics, underthe trade reference LIS331DLH. Additionally, such accelerometersadvantageously also comprise means for determining temperature, i.e.they have a built-in temperature sensor, which can assist in determiningwhether the drug product included in the drug delivery device has beenexposed to extremes of temperature likely to make it unsafe to use thedrug product. It has been found particularly advantageous if thedisplacement detection means are located as close as possible to thesource of vibrations emitted by the device.

As also indicated in preceding paragraphs, the magnetic field detectionmeans are located along the longitudinal axis of the injectable-drugdelivery device. In this way, it is possible to reduce the overallvolume of the dose control system by positioning the various detectionmeans along that longitudinal axis. A further advantage is that axialalignment avoids potential distorsions of magnetic field, as might befound if the magnetic field detection means were located, for example,perpendicularly or at an angle to said longitudinal axis, and whichwould either interfere with the measurements, or else require morecomplex calculations to take into account any such distorsion.

The interplay between the displacement detection means, the magneticfield detection means and the magnetic field production means is one ofthe interesting combinations of features of the present invention.

The dose control system also advantageously comprises an integratedcontrol unit connected to the magnetic field detection means, and to thedisplacement detection means, for processing information received fromboth the magnetic field detection means and the displacement detectionmeans. This integrated control unit can be mounted on a printed circuitboard, for example, of suitably reduced dimensions, e.g. approximately45 mm long by 15 mm wide, and 1.5 mm deep. The integrated control unithandles all electrical communication and signalling between thedifferent electronic components of the dose control system. It is alsoresponsible for execution of the dose management system and calculationsenabling precise positional locations of the magnetic field productionmeans to be calculated and determined, as well as handling signals fromthe movement detection means, the autonomous power means, thecommunication means with a local or remote data processing system, e.g.on a smartphone. It can be programmed remotely, upon first use, orreceive information and updates, in a similar way to other electronicdevices today containing integrated control units. Such integratedcontrol units are known per se, and often integrate a central processingunit, a real time clock, one or more memory storage systems, andoptionally communications systems or subsystems, along with otherdesired components.

The dose control system of the present invention marks a clear breakwith the past solutions, by providing a dose control system, that is notonly removably mounted on the body of the drug delivery device, but isalso capable of accurately providing detection of changes in angularposition due to subtle changes in magnetic field, and therebycalculating the corresponding selected dose, without having to place allof the components within the body of the drug delivery device. In fact,the dose control system of the present invention has enabled theapplicants to provide a removably mountable system, that can be usedwith a variety of different drug delivery devices currently on themarket, in particular, but not exclusively, the insulin autoinjectorpens that are currently distributed for patient self-medication.

BRIEF DESCRIPTION OF THE FIGURES

The invention will be further described in relation to the accompanyingfigures, provided for illustrative and non-limiting purposes ofexemplary manifestations of the embodiments of the present invention, inwhich:

-   FIG. 1 is a schematic view of an example of a dose control system    according to the present invention;-   FIG. 2 is schematic flow chart of the functioning of part of the    system;-   FIG. 3 is a cross-sectional schematic representation of a dose    control system according to the present invention, mounted onto an    injectable-drug delivery device, in this case, an insulin    autoinjector pen;-   FIG. 4 is a close up schematic cross-sectional representation of a    removably mountable dose control system according to the present    invention, in its unmounted or “free” state.

DETAILED DESCRIPTION

Turning now to FIG. 1 , a schematic diagram of the components of a dosecontrol system (1) according to the present invention is displayed. Sucha dose control system comprises for example, an integrated control unit(2), for example, mounted on a printed circuit board, or equivalent onwhich various components are mounted and in connection with each other.The integrated control unit (2) could also be comprised of circuitsengraved or etched in silicon or the like, as is known per se. In fact,virtually the whole dose control system could be engraved into a single,or multiple, interconnected blocks of silicon or other similarsemi-conductor material as generally known in the art if so desired. Theintegrated control unit (2) comprises a central processing unit (CPU,3), which is responsible for processing and managing signals andcommunication between the various components of the system, and also forcalculations, and execution of program code stored within the system, oroperable remotely on said system. The integrated control unit (2)additionally comprises a real time clock (RTC, 4), for keeping andmeasuring time within the dose control system. The real time clock (RTC,4) can also be integrated into the central processing unit (CPU, 3), forexample, using frequency measurements whilst the central processing unit(CPU, 3) is powered with energy, in order to calculate time and timedifferences for various events within the system. The dose controlsystem is also equipped with a communications subsystem (COM, 5), forexample a low power consuming bluetooth radio device, the communicationssubsystem allowing for the dose control system to communicate with alocal or remote data processing system (not shown), e.g. a smartphoneand corresponding smartphone application, used to provide informationand feedback to the user on usage of the dose control system.Additionally, the system also has some form of memory storage (MEM, 6),for storing information within the system, whether transiently orpermanently, such information coming from a variety of sources,including the values or signals measured or determined from otherendpoints of the system, values calculated or stored by the centralprocessing unit (CPU, 3), values or data received from the remote orlocal data processing system, such as the smartphone, factory settingsfor calibration of the system, a unique identifier means or dataidentifying the device uniquely, and the like. Such memory storagesystems (MEM, 6) are known per se to the skilled person.

The integrated control unit (2), and by extension, the centralprocessing unit (CPU, 3), is also in communication with at least oneaccelerometer (ACC, 7) and at least one magnetometer (MGR, 8). Theaccelerometer (ACC, 7) is responsible for detecting and/or measuringchanges in relative movement due to acceleration of the drug deliverydevice on which the dose control system is mounted, be it from ahorizontal to vertical position as held by the user, or any position inbetween, with regard to a set of pre-determined and pre-programmedreference positions. The accelerometer (ACC, 7) is also responsible fordetecting and/or measuring changes in relative movement due toacceleration of the drug delivery device when a user sets a dosage via adose selector shaft, which causes a vibration of the drug deliverydevice, i.e. a relative movement of acceleration, that is detectable bythe accelerometer (ACC, 7). The strength and frequency of the relativemovements of acceleration, which are communicated from the accelerometer(ACC, 7) to the central processing unit (CPU, 3) are used to determinethe type of operation that the user has effected. Such relativemovements of acceleration can include vibrations caused by clicksproduced by the drug delivery device, e.g. in the majority ofautoinjector drug delivery devices, e.g. pens, for self-injection ofvarious drugs, e.g. insulin, ATP, and the like, these clicks provide anaudible cue signal for the user to indicate various operationsundertaken by the latter, but the clicks also produce vibrations withinthe drug delivery device that can be suitably picked up by anaccelerometer.

The mangetometer (MGR, 8) is also connected to the central processingunit (CPU, 3). This component is responsible for detecting changes inmagnetic field, as produced by movement of the magnet (MAG, 9) which isin a movable spaced relationship with the magnetometer (MGR, 8). Themagnetometer is capable of detecting changes of magnetic field alongmultiple axes, for example one, two, three or more axes, althoughdetection of changes in magnetic field along two or three axes arepreferred. Usually, these axes are perpendicular to one another, so asto provide a three-dimensional magnetic field detection zone. The atleast one, and preferably two, magnetometers are located so as to beable to detect corresponding changes in magnetic field as the magnet(MAG, 8) is displaced. As the drug delivery device on which the dosecontrol system is mounted has a longitudinal axis, it is preferable toalso locate the at least one magnetometer (MGR, 7) along saidlongitudinal axis. In a preferred embodiment, the system includes twomagnetometers and these are located in axial alignment along thelongitudinal axis of the drug delivery device when the dose controlsystem is mounted on said device. This allows the dose control system toremain compact in size and dimensions, and thereby not negativelyinfluence or interfere with normal, habitual manipulation of the drugdelivery device by the user. The magnetometer is also suitablyconfigured to detect the earth’s magnetic field, and any changes thereinthat might occur when the user travels with the drug delivery device, asthe earth’s magnetic field, and changes therein can influence themeasurements made by the magnetometer (MGR, 7) in regard to the magneticfield producing means of the dose control system.

The magnetic field producing means in the present exemplary deviceinclude a magnet (MAG, 9). In one particularly preferred embodiment, themagnet produces a three dimensional magnetic field along threeperpendicularly positioned axes (x, y, z). As mentioned above, themagnetometer (MGR, 7) detects changes in magnetic field produced by themagnet (MAG, 9), when the latter is displaced proximally, and away from,or distally and towards, a proximal extremity of the drug deliverydevice. This detection of magnetic field changes occurs without any formof electrical or electronic or physical contact between themagnetometer(s) (MGR, 7) and the magnet (MAG, 9), leading to thedesignation of the dose control system as a contactless system. Themagnet preferably has a substantially annular shape, with a hole in themiddle, and can be made of any suitable magnetic or magnetizablematerial, details of which are given elsewhere in the presentspecification. The magnet (MAG, 9) can thus be mounted on a doseselector shaft of the drug delivery device, which is in longitudinalaxial alignment with both the longitudinal axis of the drug delivereddevice and the magnetometer(s). The dose selector shaft is generally rodshaped, such that the substantially annular magnet can be removably slidonto the shaft, and produce a three-dimensional magnetic field aroundthe proximal extremity of the drug delivery device. The magnet isremovably mounted on the dose selector shaft in such a way that it canimpart rotational movement to said shaft when turned by a user. Rotationcan occur in both clockwise and counter-clockwise directions. The magnethas two opposing poles, each substantially constituting a half, orhemi-spherical part of the annular magnet. As the magnet rotates, theopposing poles also rotate about the longitudinal axis of the device. Afirst reference point of known magnetic field strength along one, two orthree axes, is detected by the magnetometer(s) and this information isstored in the dose control system, for example in memory (MEM, 6), viathe central processing unit (CPU, 3). Generally, this first positionwill correspond to a position of the magnet (MAG, 9) in which it isclosest to the proximal extremity of the drug delivery device, andbeyond which further rotation of the dose selector shaft in a givendirection is impossible. When the user rotates the magnet (MAG, 9), inan allowed direction of rotation, and correspondingly indexed rotationalmovement of the dose selector shaft, the magnet and proximal extremityof the dose selector shaft move longitudinally in a proximal directionaway from the proximal extremity of the body of the drug deliverydevice, but along the longitudinal axis of the device in general. As themagnet (MAG, 9) rotates around said longitudinal axis, and translatesthere along, changes in magnetic field and polarity are detected by thesuitably positioned magnetometer(s) (MGR, 8). The variations in magneticfield can be resolved into mathematical components comprising vectorsand moduli by the central processing unit (CPU, 3), and therefrom anangular position of rotation calculated, allowing for extremely precisedetermination of the angular position and distance of the magnet withrespect to the magnetometer(s) MGR, 8). These positions are correlatedto a dose selected or selectable by the user in a lookup table which ispreferably stored within the system, or alternatively stored within aremote data processing unit, such as a smartphone, wherein the maximumand minimum distances of allowed travel and rotation of the magnet (MAG,9) along the longitudinal axis correspond to the maximum and minimumdosages allowed by the drug delivery device. In this way, the dosecontrol system is able to present to the user an exact representation ofthe dose selected by the user at any given rotational and translationalmovement point of the magnet (MAG, 9), without interfering or changingthe usual modus operandi of the drug delivery device. In an exemplarydose control system of the invention, the magnetometer(s) are configuredto be able to detect magnetic fields from between ±4 gauss to ±16 gauss,with a sensitivity, or resolution, of between about 6842 LSB/gauss at ±4gauss to about 1711 LSB/gauss at ±16 gauss. This means that the dosecontrol system preferably has a resolution that is able to detectchanges in magnetic field corresponding to an angular rotation of themagnet and dose selector shaft of 0.9° about the longitudinal axis, butas mentioned above, the resolution and sensitivity of the variouscomponents can be configured to correspond to any drug delivery devicethat functions in the same way via a rotatable dose selector shaft.

Also represented in FIG. 1 are a power supply (POW, 10), which isgenerally a portable, autonomous power supply, for example, one or morebatteries, or rechargeable power elements, capable of supplyingsufficient electrical power to the entire system, even when for example,the device is not being directly manipulated. The integrated controlunit (2) can additionally comprise a power management unit, thatregulates power supply voltage to the system, including its variouscomponents, in order to maximise the longevity of said autonomous powersupply. The power supply can also communicate with a user-activatedwake-up button (WAK, 11) which allows the dose control system to bewoken up by the user from a hibernating or sleeping state.

The dose control system can also further comprise a light emittingsignal (LIG, 12), for example, a LED, which indicates a status of thedevice according to detected events or conditions and managed by thecentral processing unit (CPU, 3), e.g. green, red, blue and white colouremission, each colour corresponding to a certain state or condition ofthe dose control system.

In yet a further embodiment, the dose control system can also comprisean alarm (ALA, 13) system, in communication with the central processingunit (CPU, 3), which can be configured to emit an audible alarm, say, inthe case of malfunction of the system, or in the case of a failedinjection, or for any other suitable condition or event detected withinthe system.

FIG. 2 is a schematic block diagram representation of the functioning ofa dose control system according to the invention. In a first step, wheelclick detection (14) of the rotating dose selector shaft is effected bythe accelerometer, as the click generates vibrations which are picked upby the accelerometer (ACC, 7). The magnetic field values detected (15)by the magnetometer(s) (MGR, 8) of the magnet (MAG, 9) which rotates atthe same time as the dose selector shaft are then read into the centralprocessing unit (CPU, 3). Next, the angle and modulus of the magneticfield are calculated (16) by the central processing unit (CPU, 3). Thesevalues are correlated with, or compared to (17) a predetermined set ofvalues that has been preprogrammed into the dose control system.Finally, a determination (18) of the selected dose is made. These stepsare repeated as necessary, each time the user causes the dose selectorshaft to rotate about the longitudinal axis. Once the user has decidedwhich dose it wishes to inject itself with, a click caused by the userpressing a proximally located injector end button, which causes avibration and corresponding movement of acceleration within the drugdelivery device, is registered by the accelerometer. The frequency, orinterval between each end button click is used to determine whether aninjector button click is compared to a known list of pre-determinedmovements of acceleration to determine whether the end button click wasintentional, or else the result of accidental activation of the endbutton or movement in the drug delivery device. If the movement ofacceleration and frequency thereof do correspond to a situation in whichthe dose is recognized as having been deliberately selected, ready forinjection, this dose is registered within the system, e.g. withinmemory, and communicated via the communication means to the dataprocessing unit, for example, a smartphone application, along with thetime at which said event occurred. In this way, the smartphoneapplication is able to process that information and provide it to theuser in the form of tracking or observance information.

FIG. 3 is a schematic cross-sectional representation of a dose controlsystem mounted on an injectable-drug delivery device, indicatedgenerally by the reference numeral 20. The injectable-drug deliverydevice (20) generally comprises a substantially elongate drug deliverybody (21), having a longitudinal axis (25), at least one injectable drugheld by the body (not shown), usually within a cartridge, the body (21)having a distal extremity (23) and a proximal extremity (22), and anouter peripheral surface (24). In FIG. 3 , at the distal extremity (23),a cap (26), similar to a pen cap, is provided to cover the otherwiseexposed needle and prevent the user from accidentally stabbing orotherwise injuring themselves. The drug delivery device furthercomprises, at the proximal extremity (22), a dose selector shaft (27),which is connected to a dose selector wheel (28), rotatable about thelongitudinal axis, and an end button which can be pressed by the user toarm the device, thereby validating a selected dose, and effect druginjection via usual, known methods and means. This type of drug deliverydevice is similar to majority of drug delivery devices known to theskilled person.

The dose control system is indicated in FIG. 3 by the general referencenumeral 30. As is apparent from FIG. 3 , the dose control system (30) islocated substantially at a proximal extremity of the drug deliverydevice (20), and is positioned on and around the outer peripheralsurface (24) of the body of said device. In this particular example, thecentral processing unit (CPU, 3), real time clock (RTC, 4), storagememory (MEM, 6) and communications subsystem or communication means(COM, 5) are located on a printed circuit board to form the integratedcontrol unit (2) which is encased within a polymer resin block (31). Thedose control system has an autonomous power supply (POW, 10) in thisexample and FIGS. 3 and 4 illustrated as two batteries (32, 33), forexample lithium ion batteries. The dose control system further comprisesmagnetic field producing means (MAG, 9), illustrated in FIG. 3 as asubstantially annular shaped object which is located at the proximalextremity (22) of the device, and in a proximally spaced relationship tosaid extremity (22), whereby the magnet (MAG, 9) is removably mounted onthe dose selector wheel (28), which in turn is connected to the doseselector shaft. As the wheel (28), shaft (27) and magnet (MAG, 9) can becaused to rotate around the longitudinal axis (25) of the drug deliverydevice (20), the magnet (MAG, 9) will be displaced both rotationallyaround said axis thereby also effecting a translational movement awayfrom, in a proximal direction, or alternatively, towards, i.e. in adistal direction, the proximal extremity of the body (21) of the drugdelivery device (20). The maximum distance of linear travel of the wheel(28), shaft (27) and magnet (MAG, 9), will generally substantiallycorrespond to the maximum allowable dose that can be injected, and alsotherefore correspond to the maximum distance of travel of a piston thatis usually provided to eject the drug from the cartridge in which it isheld. As an example, the position nearest to the proximal extremity ofthe body of the drug delivery device will correspond to either no dose,or the minimum dosage. The wheel (28), shaft (27) and magnet (MAG, 9)will be blocked from rotating in a direction that would be likely tobring the latter even closer to the proximal extremity (22) of the body(21). In the opposite direction, however, i.e. in the proximaldirection, the wheel (28), shaft and magnet will be able to be caused torotate, e.g. via a user turning the magnet (MAG, 9) and wheel (28) withtheir fingers as many times as is allowed by the configuration of thesystem, and corresponding to the maximum dosage that can be injected. Asthe magnet, and wheel are turned, the shaft also rotates, and generatesan audible clicking sound. The audible clicks correspond to a movementof acceleration transmitted through the body of the device and detectedby the accelerometer (7). The rotation and longitudinal displacement oftravel of the magnet (MAG, 9) causes changes in the produced magneticfield which are detected by the magnetometers (34, 35). The valuesdetected by the magnetometers (34, 35) are communicated to the centralprocessing unit (CPU, 3), and used to calculate angular position of themagnet (MAG, 9) and wheel (28) on the dose selector shaft (27) andthereby determine the dose which has been selected by the user. Primingof the injector system, via a push from the user on the end button (29),which also raises an audible click, and a corresponding linear movementof acceleration along the longitudinal axis of the device (20), isregistered by the accelerometer (7). The central processing unit (CPU,3) calculates the frequency and number of clicks produced and comparesthem to stored values in a lookup table to determine whether or not thedevice is effectively primed for injection, and if it is determined bythe central processing unit that such is the case, the value of thecalculated dose obtained from the changes in magnetic field is stored inmemory (MEM, 6) and validated as the dose selected for injection. Thisvalue is then communicated via the communication means (COM, 5) to thesmartphone application.

The magnetic field detectors can be configured to function in variousways. For example, in a serial configuration of magnetometers, i.e. whenthe magnetometers are aligned axially along the longitudinal axis, in aspaced apart relationship, and when the magnet (MAG, 9) is closest tothe proximal extremity of the body (21) of the drug delivery device, theforce of the magnetic field produced by the magnet can exceed the upperlimit of the magnetometer (8 a) closest to the magnet. In such a case,the magnetomer (8 a) is considered to be “saturated”. At this point, itis unnecessary to factor in any values detected by the secondmagnetometer (8 b), since saturation of the first, proximal magnetometer(8 a) allows for complete resolution of the angular moment and moduluswhen the magnet is rotated about the longitudinal axis. If the doseselector shaft is designed to also effect lateral displacement alongsaid longitudinal axis, proximally, and away from said proximalextremity, as the magnet also moves away proximally, so does thesaturation of the first proximal magnetometer (8 a) drop. Once apredetermined level of magnetic field has been reached, the system isconfigured to activate the second, more distal magnetometer (8 b), sothat both magnetometers (8 a, 8 b) can be used to effect fine detectionof smaller and smaller changes in magnetic field and angular moment,including taking into account any effects due to the earth’s ownmagnetic field which, at the earth’s surface is generally between 0.25and 0.65 gauss. In a similar and reverse manner, when the dose selectorshaft, and magnet, move distally back towards the proximal extremity ofthe body of the device, the second, more distal magnetometer (8 b) canbe automatically switched off when a predetermined higher level ofmagnetic field is detected. In an alternative, parallel, configuration,on the other hand, both magnetometers (8 a, 8 b), whilst still alignedalong the longitudinal axis of the drug deliver device, are bothoperational throughout all of the displacements of the magnet, and allchanges in magnetic field are detected by both magnetometers (8 a, 8 b).

FIG. 4 is a schematic cross-sectional representation of a housingsuitable for including the dose control system of the present inventionand illustrating one of several ways in which the dose control systemcan be mounted on an injectable-drug delivery device such as thosecurrently known. Reference numerals remain the same between FIGS. 3 and4 for like elements of the dose control system. The housing (35 a, 35 b)is designed to encase and enclose the drug delivery device (20), aroundand along its longitduinal axis (25) and sits removably on a peripheralouter surface (24) of said device (20). The housing is designed to snapor push fit onto the device (20) and preferably comprises at least twomating components, which engage with each other and encase the devicealong its body (21), along the longitudinal axis (25), at a proximalextremity (22) thereof. The housing (35 a, 35 b) further comprises gripfacilitating means, for example a zone (36 a, 36 b) of compressibleelastomer, locate on an inner wall of the housing, and which facilitatesand increases the grip of the housing containing the dose system on theouter peripheral surface (24) of the body (21) of the drug deliverydevice (20) to provide a snug fit that will prevent the housing (35 a,35 b) from moving relative to the body of the drug delivery device untilsuch time as the housing is to be removed, for example, if the drugdelivery device malfunctions, or the cartridge is empty or quite simplyif it is desired to switch the dose control system to another drugdelivery device (20). The housing is designed preferably to be snap fit,enabling it to be removed according to a predetermined set of steps,wherein each part of the housing (35 a, 35 b) is removed according to asequence, without destroying or damaging the dose control system (30)contained therein, or the drug delivery device (20). The zone ofcompressible elastomer (36 a, 36 b) can further comprise compressionfacilitating ridges or dips (37 a, 37 b), i.e. added or removedelastomeric material in spaced apart arrangement along the the lengthand breadth of the zone (36 a, 36 b) so as to increase or decrease gripof the housing (35 a, 35 b) on the outer peripheral surface (24) of thedevice (20). The housing (35 a, 35 b) additionally provides a window(39) allowing a user to see an analog or digital representation of theselected dose, which is generally located and displayed on the outerperipheral surface (24) of the body (21) of the drug delivery device(20). The dose control system containing the magnetic field producingmeans (MAG, 9) is housed in a separate housing (38) that is located, andfits snugly with, the wheel (28). This magnet housing (38) is designedin a similar way to the housing (35 a, 35 b) of the other components ofthe dose control system to able to be removably snap or push fit ontothe wheel (28) of the dose selector shaft (27) and can alsoadvantageously comprise grip facilitating means, for example a zone ofelastomeric material enabling the magnet housing (38) to surround andencase the wheel (28).

What is claimed is:
 1. A dose monitoring system for mounting on aninjection pen having a body and a dose setting wheel defined at the endof the body, the dose monitoring system comprising : a magnet configuredto be attached to an outer surface of the dose setting wheel; a housingconfigured to be attached to an outer surface of the body of theinjection pen, the housing comprising an integrated control unit and atleast one magnetometer in electrical connection with said integratedcontrol unit ; the integrated control unit, when the housing is mountedon the injection pen, being configured to register at least one magneticfield sensed by the at least one magnetometer when the magnet co-rotateswith the dose setting wheel during setting of a dose by a user on theinjection pen ; the integrated control unit being further configured,when the housing is mounted on the injection pen, to calculate a doseset by the user of the injection pen from the at least one magneticfield registered with said integrated control unit.
 2. Dose monitoringsystem according to claim 1, wherein the at least one magnetometer islocated in the housing, and when mounted on the injection pen, isaligned parallel to a longitudinal axis of the injection pen.
 3. Dosemonitoring system according to claim 1, wherein the at least onemagnetometer includes two magnetometers, and when mounted on theinjection pen, the two magnetometers are aligned with each other, and inparallel to,a longitudinal axis of the pen.
 4. Dose monitoring systemaccording to claim 1, wherein the housing, comprises a body portionconfigured to engage and surround at least a part of a circumference ofthe body of the injection pen.
 5. Dose monitoring system according toclaim 1, wherein the housing comprises a communications unit, inelectrical connection with the integrated control unit, and configuredto communicate a dose set by a user as calculated by the integratedcontrol unit, to a remote and/or local data processing system.
 6. Dosemonitoring system according to claim 1, wherein the housing comprises acommunications system, in electrical connection with the integratedcontrol unit, and configured to communicate a dose set by a user, ascalculated by the integrated control unit, to a smartphone.
 7. Dosemonitoring system according to claim 1, wherein the housing comprisesone or more of a real time clock, a memory, a battery power supply, alight emitting signal, an audible alarm, a wake-up button, and anaccelerometer, all in electrical connection with the integratedprocessing unit.
 8. Dose monitoring system according to claim 1,wherein, when mounted on the injection pen, the integrated control unitis configured to determine an operational status of the injection pencomprising one or more of a movement of acceleration of the injectionpen, a purge position of the injection pen, an injection position of theinjection pen, a temperature of a drug held within the body of theinjection pen, a determination of acceptable temperature operatinglimits for a drug held within the body of the injection pen, adetermination of a level of battery power supply, and a determination ofa hibernated or an awake state of the dose monitoring system.
 9. Dosemonitoring system according to claim 1, wherein the magnet is configuredto be attached to the outer surface of the dose setting wheel includedat a proximal end of the injection pen.
 10. Dose monitoring systemaccording to claim 1, wherein when mounted, the housing is configured tobe attached to the outer surface of the body of the injection penadjacent a proximal end of the body of the injection pen.